# A highly potent and broadly accessible bispecific nanobody for the treatment of ebola virus infections

## TL;DR

A new bispecific nanobody was developed to treat Ebola virus infections, offering high potency and easy delivery without injections or refrigeration.

## Contribution

A novel bispecific nanobody combining two single-domain antibodies is introduced for improved Ebola virus treatment.

## Key findings

- A single dose of the bispecific nanobody provided strong protection in EBOV-infected mice.
- The nanobody can be administered intranasally, eliminating the need for injections.
- It is highly stable at room temperature, allowing refrigeration-free deployment.

## Abstract

Ebola virus (EBOV) causes recurring outbreaks, with a case fatality rate of about 40%. Currently approved vaccine and antibody therapies face major limitations, including only modest reductions in mortality and restricted accessibility due to their reliance on injection-based delivery and cold-chain transport and storage. To address these challenges, we developed a bispecific nanobody, Nanosota-EB1/EB2-Fc, composed of two nanobodies (camelid-derived single-domain antibodies, Nanosota-EB1 and Nanosota-EB2) that target distinct epitopes on the EBOV glycoprotein (GP) and are fused to a human Fc domain. Through cooperative contributions from both nanobodies, this bispecific nanobody strongly inhibits GP function and effectively overcomes the virus’s decoy mechanism. A single dose provided strong protection in EBOV-infected mice, including when administered at late stages of infection. It was also effective when administered intranasally, offering a needle-free delivery option. Furthermore, its high in vitro stability indicates that it can be deployed without refrigeration. Taken together, this novel bispecific nanobody represents a promising next-generation therapeutic for EBOV, combining high potency with broad accessibility.

Ebola virus (EBOV) remains a significant global health threat, with current treatments providing only modest survival benefits and limited accessibility due to their dependence on injection and cold-chain transport and storage. Here we developed a novel bispecific nanobody, Nanosota-EB1/EB2-Fc, which combines two nanobodies (single-domain antibodies) targeting distinct epitopes on the EBOV glycoprotein. Through intramolecular cooperativity, Nanosota-EB1/EB2-Fc inhibits glycoprotein function and evades the virus’s decoy mechanisms. A single dose showed strong therapeutic efficacy in EBOV-infected mice, including when administered at late stages of infection. Nanosota-EB1/EB2-Fc is also suitable for intranasal administration and exhibits high in vitro thermostability, enabling needle-free delivery and refrigeration-independent deployment. Together, these features position Nanosota-EB1/EB2-Fc as a highly potent and broadly accessible therapeutic candidate for future EBOV outbreaks.